Antispasmodic compound and process of producing the same



Patented Mar. 4. 1924- UNITED 'STATES' PATENT OFFICE.

WILLIAM H. ENGELS, F RAHWAY, NEW JERSEY ASSIGNOR TO MERCK & (30., 0F

' NEW YORK, N. Y., A CORPORATION OF NEW YORK.

'amsrasmomc comrotmn AND PROCESS or rnonucmo THE sum No Drawing. Original application filed April 25, 1922, Serial No. 556,424. Divided and this application filed May 13, 1922.

lthough benzyl sulfuric acid, benzyl phosphoric acid, benzyl succinic acid and .benzyl phthalic acid have been mentioned in chemical literature as laboratory products (Beilstein II, p. 1050; II. Erg., pp. 638 and I5 1048; Berichte, 35, p. 4078), none of them has, sofar as I know, received any industrial application,and particularly none in the'therapeuticart;

So far as 1' know, in the only benzylesters whidrhave heretofore received any indusli1'ifl1 or therapeutic application (e. g., benzylbnzoiitmbenzylcinnamate, dibenzyl suec1nate,.benzylsalicylate, and others the acid group has been fully saturated by the benzyl group or groups, and a heretofore insurmountable obstacle to their use hypodermically has been their insolubility in water, 1n

consequence of .which their therapuetic use I has been substantially limited to administra- ":20 tion per os.

I have produced, for the' first time, benzylester compounds and, specifically, alkali benzyl= phthalates, especially sodium benzyl phthalate, of a water-solubility and purity compatible with hypodermic, intravenous and subcutaneous use, anda process by which .they may be obtained, anl I believe that I have not merely convdiit'eld; certain unused substances into products ofgreat utility but have greatly enlarged the medicinally important field of antispasmodic remedies.

My invention alsoinvolvesthe. discoverv of the conditions under which any.'by-products that .may be present with the unsaturated benzyl phthalate are eliminated at the same time that the ester is transformed into a water-soluble condition, so that I obtain a therapeutically pure water-soluble; benzyl phthala-te.

, application SorialNo. 556,424, which was My present application is a divisionof Serial No. 560,719.

filed in the United States Patent Oflice on or about April 25, 1922.

To explain one method by which my invention mav be carried out, the following example is givenz 1 kilo am of phthalic acid monobenzylester is issolved in 7 litres alcohol and neutralized with the required amount of sodium hydroxide or carbonate, applying heat to the mixture at the same time. The white sodium salt separatesout as a bulky mass upon coolingl z In the illustrative example, the formation of the salt may be said to be under approximately anhydrous conditions, because the water present in the 70% alcohol is only sufficient to enable the by-products tobe re tained in--the solvent,-,su'ch by-products in this instance being more or less insoluble in to alcohol alone. In the illustrative example r of my process, I have mentioned sodium hydroxide or carbonate as the neutralizing compounds. It will be understood, .how-' ever, that other alkali compounds, such, for 7: example, as ammonium, potassium or lithium hydroxide or carbonates are to be considered as equivalents.

What I claim and desire to'secure by Letters Patent of the United States is: p

so 1. As an antispasmodic adapted for hypodermi'c injection, a therapeutically pure .alkali benzyl phthalate.

2. As an antispasmodic adapted for hypodermic injection, therapeutically pure sodium benzyl phthalate.

The process of making an alkali benzyl phthalate which consists intreating phthalic acid monobenzylest'er withan alkali base under approximately anhydrous conditions and isolating the salt.

4. The process of simultaneously urifying and rendering water-soluble p thalic acid partially saturated by a benzyl group, which consists in completing the saturation by combination with an alkali under .ap-

proximately anhydrous conditions.

WILLIAM H. ENGELS.

lrVitnemesr R. E. Gnomes,

F. W. Hmmnnsaorr. 

